Keytruda under fire as oncologists push lower doses to cut soaring cancer costs

US pharma giant Merck & Co, maker of blockbuster cancer drug Keytruda, is facing growing criticism from oncologists who say company policies on dosing and packaging are inflating treatment costs and forcing patients to buy significantly more medicine than needed.

Now widely used across multiple cancers, Keytruda generated $29.5 billion in 2024 after first winning approval from the US Food and Drug Administration in 2014 for metastatic skin cancer. Last year, it was added as a first-line treatment for metastatic non-small cell lung cancer, cervical cancer and colorectal cancer to the World Health Organization Model List of Essential Medicines.

Yet, despite its clinical success, specialists in India say the drug remains financially out of reach for most patients. Several oncologists told The Indian Express, as part of an investigation with the International Consortium of Investigative Journalists, that lower dosing, shorter treatment duration, vial-sharing and pooled procurement may be the only practical path until generic competition arrives, expected by 2028.

Financial toxicity of treatment

The WHO expert committee itself acknowledged the challenge, warning that immune checkpoint inhibitors like Keytruda may be unaffordable for many countries due to high prices, diagnostic costs and pressure on fragile health systems.

Dr Atul Batra, Additional Professor of Oncology at AIIMS Delhi, described the problem as “financial toxicity”, where life-saving therapies are priced beyond the reach of ordinary patients.

Debate over high fixed doses

When Keytruda was first approved in 2014, the recommended dosage was 2 mg/kg every three weeks. By 2016, after approval for lung cancer, that shifted to a flat 200 mg every three weeks for all patients, regardless of body weight.

For many Indian patients weighing between 55 kg and 65 kg, doctors say a weight-based dose would require far less medicine than the standard flat dose.

Dr Batra said immunotherapy works differently from chemotherapy, making higher doses unnecessary once all receptors are saturated. “A higher dose does not mean more cancer cells are killed,” he said, arguing that biologically effective dosing should guide treatment rather than maximum tolerated dose models used in chemotherapy.

A 2017 analysis noted that early clinical trials had already shown full receptor saturation at just 1 mg/kg, with later studies finding no major difference in effectiveness between 3 mg/kg and 10 mg/kg doses.

AIIMS study finds lower dose effective

Dr Batra and his team at AIIMS studied 157 women with triple negative breast cancer, an aggressive form resistant to hormone therapy. Patients received either standard chemotherapy or chemotherapy plus a flat 50 mg dose of Keytruda every six weeks — just one-eighth of the commonly prescribed 200 mg dose.

The results were significant. Invasive cancer was absent in 53.8% of patients who received Keytruda with chemotherapy, compared with 40.5% in the chemotherapy-only group. Among patients who underwent surgery, 56.7% showed no invasive cancer, against 41% in the chemotherapy-alone group.

“We have now demonstrated that the low 50 mg dose every six weeks can be as effective as the full 200 mg dose every three weeks,” Dr Batra said. “There is no trial comparing both directly. Who will fund it?”

Access barriers remain

Doctors say two major hurdles block wider adoption of low-dose treatment.

First, patients prescribed 50 mg cannot access Kiran, the company’s patient assistance programme, which covers only the approved 200 mg dose. That makes lower-dose treatment financially impractical for many.

Second, the drug is sold only in 100 mg vials after the company withdrew its 50 mg formulation. In a 2018 letter to the FDA, Merck said the discontinuation was for “business reasons only” and not linked to quality or safety concerns.

Dr Amol Akhade, oncologist at Nair Hospital, said refusal to recognise weight-based dosing appears commercially driven.

“If they acknowledge it works, then the question arises why a fixed dose was given for so many years,” he said.

Patients losing out

Pointing to the outpatient queue, Dr Akhade said nearly 70 out of every 100 patients with solid tumours could potentially benefit from Keytruda, but most are never even offered the option because the treatment is unaffordable.

Another Delhi-based oncologist said even when doctors prescribe the 200 mg dose so patients can qualify for assistance programmes, hospitals cannot safely store opened vials to administer smaller doses later, leading to wastage.

For thousands battling cancer, specialists say the science may support lower doses — but the system still rewards higher bills.